title: A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats.
abstract: The intestinal microflora is an important cofactor in the pathogenesis of intestinal inflammation; and the epithelial cell barrier function is critical in providing protection against the stimulation of mucosal immune system by the microflora. In the present study, therapeutic role of the antibacterial drugs rifampicin and ciprofloxacine were investigated in comparison to spironolactone, an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis of the rats. Drugs were administered for 14 days following induction of colitis. All drug treatments ameliorated the clinical hallmarks of colitis as determined by body weight loss and assessment of diarrhea, colon length, and histology. Oxidative damage and neutrophil infiltration as well as nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α) expressions that were increased during colitis, were decreased significantly. Rifampicin and ciprofloxacin were probably effective due to their antibacterial and immunomodulating properties. The multidrug resistence gene (MDR1) and its product p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). In the present study, findings of the P-gp expression were inconclusive but regarding previous studies, it can be suggested that the beneficial effects of rifampicin and spironolactone may be partly due to their action as a P-gp ligand. Spironolactone has been reported to supress the transcription of proinflamatory cytokines that are considered to be of importance in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR) inducer; thus, inhibition of the expression of NF-κB and TNF-α, and amelioration of inflammation by spironolactone suggest that this may have been through the activation of PXR. However, our findings regarding PXR expression were inconclusive. Activation of PXR by spironolactone probably also contributed to the induction of P-gp, resulting in extrusion of noxious substances from the tissue.
authors.affiliation: Department of Pharmacology, Marmara University School of Pharmacy, Istanbul, Turkey. dulgergul@yahoo.com; haletoklu@yahoo.com.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Toklu
authors.forename: L
authors.initials: L
authors.lastname: Kabasakal
authors.forename: N
authors.initials: N
authors.lastname: Imeryuz
authors.forename: B
authors.initials: B
authors.lastname: Kan
authors.forename: C
authors.initials: C
authors.lastname: Celikel
authors.forename: S
authors.initials: S
authors.lastname: Cetinel
authors.forename: O
authors.initials: O
authors.lastname: Orun
authors.forename: M
authors.initials: M
authors.lastname: Yuksel
authors.forename: G A
authors.initials: GA
authors.lastname: Dulger
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B; D009195:Peroxidase / Q000378:metabolism; D000077297:Pregnane X Receptor; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D016328:NF-kappa B; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D014409:Tumor Necrosis Factor-alpha; D013148:Spironolactone; D008315:Malondialdehyde; D002939:Ciprofloxacin; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D005978:Glutathione; D012293:Rifampin